On December 9, 2024 Theratechnologies Inc. ("Theratechnologies" or the "Company") (TSX: TH) (NASDAQ: THTX), a biopharmaceutical company focused on the development and commercialization of innovative therapies, reported data from Part 3 (dose optimization, weekly dosing schedule) of its ongoing Phase 1b trial of sudocetaxel zendusortide (TH1902) – the company’s lead investigational peptide drug conjugate (PDC) – in patients with advanced ovarian cancer (Press release, Theratechnologies, DEC 9, 2024, View Source [SID1234648919]). Based on results demonstrating favorable tolerability and signals of efficacy, the Medical Review Committee, which includes study investigators and external experts, has unanimously recommended continued evaluation and exploration of higher doses.

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"We are encouraged by the tolerability and preliminary efficacy data for sudocetaxel zendusortide seen thus far in this part of the Phase 1 study, which was designed to explore dose optimization utilizing a weekly dosing schedule in a population of heavily pre-treated ovarian cancer patients," commented Christian Marsolais, Ph.D., Senior Vice President and Chief Medical Officer at Theratechnologies. "These latest results add to the growing body of evidence that our novel PDC technology can deliver a toxic payload into cancer cells with little impact on non-cancerous tissues and we believe there could be further clinical implications at a higher dose."

A total of 13 patients with advanced ovarian cancer who progressed despite prior platinum-based and taxane chemotherapy were enrolled in two Arms in Part 3 of the Phase 1b trial. Seven patients were enrolled in Arm A and received a 1.75-mg/kg/week dose of sudocetaxel zendusortide on a weekly infusion, three-weeks-on/one-week-off schedule every 28 days. The six patients enrolled in Arm B received a 2.5-mg/kg/week dose on the same schedule.

Investigators observed no dose-limiting toxicities in either arm. Although there were no responses observed in the five Arm A participants that comprised the per-protocol (PP) set, there was encouraging evidence of activity observed in three of the six patients enrolled in the Arm B PP set, including one patient with a complete resolution of a liver lesion. Those three Arm B patients also experienced significant reductions in the CA-125 ovarian tumor marker as well as significant tumor shrinkage, including two patients with more than a 25% reduction in tumor size. Additionally, Arm B participants in the PP set received a mean of 10.25 weeks of treatment compared to a mean of 7.6 weeks of treatment in patients treated on Arm A. All patients in Arm B received at least two cycles of treatment, with some completing up to four cycles (on-treatment range: 4-18 weeks).

The Company received permission from the U.S. Food and Drug Administration (FDA) in 2023 to amend the initial Phase 1b clinical trial protocol based on results from Parts 1 and 2, which utilized every-3-week dosing. For Part 3, the protocol was amended to explore dosing weekly for three weeks, followed by a one-week break and shifted the focus to patients with ovarian cancer. At the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) annual meeting earlier this year, Theratechnologies presented an updated analysis from Parts 1 and 2 of the study, in which sudocetaxel zendusortide induced durable disease stabilization (up to 45 weeks) lasting beyond treatment completion in several patients with a variety of solid tumors. The ASCO (Free ASCO Whitepaper) presentation also highlighted early signals of efficacy observed in female cancers (ovarian cancer, endometrial cancer, triple-negative breast cancer [TNBC]), as well as a manageable safety profile when sudocetaxel zendusortide was dosed at 300mg/m2 given once every 3 weeks with few Grade 3 adverse events (AEs).

"The latest data from Part 3 of the Phase 1 trial build on a compelling body of preclinical and translational evidence of antitumor activity with sudocetaxel zendusortide," said Ira Winer, M.D., Ph.D., FACOG, a member of the Gynecologic Oncology and Phase 1 Clinical Trials Multidisciplinary Teams at Karmanos Cancer Center and Professor of Oncology at Wayne State University School of Medicine in Detroit, MI. "While this is a small sample of patients, it is not often that we see promising signs of efficacy, combined with favorable safety and tolerability data, in this patient population with advanced disease. We therefore recommend and encourage continued investigation with further dose escalation for this agent."

In addition to the Phase 1b clinical trial results, there is also an extensive body of preclinical data demonstrating the flexibility of the Company’s SORT1+ Technology platform when conjugated with different toxic payloads. With a significant portion of the clinical trial data to date now available, Theratechnologies will accelerate its search for a partner to advance its oncology program.

About Sudocetaxel Zendusortide (TH1902) and SORT1+ Technology

Sudocetaxel zendusortide is a first-of-its-kind sortilin receptor (SORT1)-targeting PDC, and the first compound to emerge from the Company’s broader licensed oncology platform. A new chemical entity, sudocetaxel zendusortide employs a cleavable linker to conjugate (attach) a proprietary peptide to docetaxel, a well-established cytotoxic chemotherapeutic agent used to treat many cancers. The FDA granted Fast Track designation to sudocetaxel zendusortide as a single agent for the treatment of all sortilin-positive recurrent advanced solid tumors that are refractory to standard therapy.

Theratechnologies has established the SORT1+ Technology platform as an engine for the development of PDCs that target SORT1, which is expressed in multiple tumor types. SORT1 is a "scavenger" receptor that plays a significant role in protein internalization, sorting, and trafficking. Expression of SORT1 is associated with aggressive disease, poor prognosis, and decreased survival. It is estimated that SORT1 is expressed in 40% to 90% of endometrial, ovarian, colorectal, triple-negative breast (TNBC), and pancreatic cancers, making this receptor an attractive target for anticancer drug development.

On December 9, 2024 Rgenta Therapeutics, a clinical-stage biotechnology company pioneering the development of a new class of oral small molecules targeting RNA for oncology and neurological disorders, reported the presentation of preclinical data demonstrating anti-tumor activity of RGT-61159, a potent, selective oral small molecule inhibitor of MYB, a master oncogene in human malignancies (Press release, Rgenta Therapeutics, DEC 9, 2024, View Source [SID1234648935]). The data, which are being presented at the 66th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition being held December 7-10, 2024, in San Diego, CA, support the development of RGT-61159 as a potential treatment for acute myeloid leukemia (AML).

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"As demonstrated by the data being presented at ASH (Free ASH Whitepaper), RGT-61159 leads to the elimination of MYB RNA and protein in cancer cells and results in significant anti-tumor activity," said Simon Xi, Ph.D., co-founder and chief executive officer of Rgenta. "Importantly, RGT-61159 is active in a range of AML models harboring the most prevalent genetic alterations found in patients that often lead to resistance to current treatments. These data support our plans to extend our clinical development of RGT-61159 beyond our existing programs in solid tumors, adenoid cystic carcinoma (ACC) and colorectal cancer (CRC), and into hematologic malignancies such as AML."

RGT-61159 is a potent, selective oral small molecule inhibitor of the MYB oncogene that functions by inducing the inclusion of a cryptic exon into MYB RNA transcripts, resulting in the activation of the nonsense mediated decay pathway and promoting MYB mRNA depletion and thus, MYB protein degradation. The data presented at ASH (Free ASH Whitepaper) demonstrate that RGT-61159 potently eliminates MYB RNA and protein in a dose-dependent manner in AML cancer cell lines. As a single agent, RGT-61159 showed significant anti-tumor activity in several AML cell line-derived xenograft (CDX) models that harbor the most prevalent genetic alterations found in patients. In addition, RGT-61159 driven MYB inhibition led to a robust, dose-dependent increase in the differentiation markers CD11b and CD14 on the surface of THP-1 AML cells and the reduction of master oncogenes such as MYC and BCL2 across a broad panel of AML cell lines, providing a strong rationale for its development as a treatment for patients with AML.

"Genomic analyses of different AML cell lines treated with RGT-61159 shed further light on key oncogenes including BCL2 and MYC that are significantly regulated by MYB inhibition and further demonstrate RGT-61159’s anti-tumor activity of leukemic cells is driven by inhibition of MYB signaling," said Travis Wager, Ph.D., co-founder, president and chief scientific officer. "These data also confirm the role of MYB as a convergent dependency across AML tumors and highlight the potential of RGT-61159, a best-in-class MYB inhibitor, as a novel therapeutic approach to address this malignancy."

About RGT-61159
RGT-61159 is an orally available small molecule designed to specifically modulate splicing of the transcription factor MYB resulting in the inhibition of the oncogenic MYB protein production, which has the potential to induce cell death of the cancer cells overexpressing MYB protein. MYB acts as a master regulator of cell proliferation, self-renewal, and differentiation processes and its aberrant expression has been demonstrated in multiple forms of human cancer including adenoid cystic carcinoma (ACC), acute myeloid leukemias (AML), T-cell acute lymphoblastic leukemias (T-ALL), colorectal cancer (CRC), small cell lung cancer (SCLC) and breast cancer. Rgenta is evaluating RGT-61159 in an ongoing multi-center, open-label Phase 1a/b clinical trial in patients with advanced relapsed or refractory ACC or CRC. The Phase 1a/b study is designed to evaluate safety, tolerability, pharmacokinetics and target engagement and clinical efficacy of RGT-61159 in patients with ACC or CRC. Additional information about the Phase 1a/b clinical trial can be accessed at ClinicalTrials.gov (NCT06462183).

About Acute Myeloid Leukemia (AML)
AML is a blood cancer that starts in the bone marrow, begins to make large numbers of abnormal cells, is characteristically fast growing, and moves quickly into the blood. AML is the most common type of acute leukemia in adults, and it accounts for about 10% of all new blood cancers each year. In the United States, there are about 20,000 new cases of AML per year. The average age of people diagnosed with AML is 68 years old, and while it is uncommon in people under 45, it can occur in adolescents and children. While complete remission can be achieved in up to 70% of patients with newly diagnosed AML, prognosis remains poor with only approximately 32% of patients that remain alive 5 years after diagnosis. Allogeneic hematopoietic cell transplantation (HCT) remains the only potentially curative strategy for most patients. Up to 40% of patients relapse after allogeneic HCT, and 5-year overall survival (OS) rates for these patients are low, approximately 30–40%.

On December 09, 2024 MAIA Biotechnology, Inc., (NYSE American: MAIA) ("MAIA", the "Company"), a clinical-stage biopharmaceutical company developing targeted immunotherapies for cancer, reported that it has entered into definitive agreements for the purchase and sale of an aggregate of 507,364 shares of common stock at a purchase price of $1.872 per share, in a private placement to accredited investors and certain Company directors (Press release, MAIA Biotechnology, DEC 9, 2024, View Source [SID1234648951]). Each share of common stock is being offered together with a warrant to purchase one share of common stock at an exercise price of $2.08 per share, which price represents the greater of the book or market value of the stock on the date the definitive agreements were executed (subject to customary adjustments as set forth in the warrants). The warrants are exercisable commencing six months following issuance and have a term of five years from the initial exercise date. The securities being sold to the Company director participating in the offering are being issued pursuant to the Company’s 2021 Equity Incentive Plan. The private placement is expected to close on or about December 11, 2024, subject to the satisfaction of customary closing conditions.

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The gross proceeds from the offering are expected to be approximately $950,000, prior to offering expenses payable by the Company. The Company intends to use the net proceeds received from the sale of the Securities to fund manufacturing of THIO for Phase II clinical trials and for working capital.

The securities described above are being offered in a private placement under Section 4(a)(2) of the Securities Act of 1933, as amended (the "Securities Act"), and/or Regulation D promulgated thereunder and, along with the shares of common stock underlying the warrants, have not been registered under the Securities Act, or applicable state securities laws. Accordingly, the warrants and underlying shares of common stock may not be offered or sold in the United States except pursuant to an effective registration statement or an applicable exemption from the registration requirements of the Securities Act and such applicable state securities laws.

This press release shall not constitute an offer to sell or a solicitation of an offer to buy these securities, nor shall there be any sale of these securities in any state or other jurisdiction in which such offer, solicitation or sale would be unlawful prior to the registration or qualification under the securities laws of any such state or other jurisdiction.

On December 9, 2024 Protara Therapeutics, Inc. (Nasdaq: TARA) ("Protara"), a clinical-stage company developing transformative therapies for the treatment of cancer and rare diseases, reported that it has commenced an underwritten public offering of shares of its common stock or, in lieu of issuing common stock to certain investors, pre-funded warrants to purchase shares of its common stock (Press release, Protara Therapeutics, DEC 9, 2024, View Source [SID1234648887]). All of the shares of common stock and pre-funded warrants to be sold in the proposed offering will be offered by Protara. In addition, Protara expects to grant the underwriters a 30-day option to purchase additional shares of common stock at the public offering price, less underwriting discounts and commissions. The proposed offering is subject to market and other conditions, and there can be no assurance as to whether or when the offering may be completed, or the actual size or terms of the offering. Protara intends to use the net proceeds received from the offering to fund the clinical development of TARA-002, as well as the development of other clinical programs. Protara may also use the net proceeds from the offering for working capital and other general corporate purposes.

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TD Cowen, Cantor, LifeSci Capital, Oppenheimer & Co. and Scotiabank are acting as joint book-running managers of the proposed offering.

The shares of common stock and the pre-funded warrants will be issued pursuant to a shelf registration statement on Form S-3 (File No. 333-275290) that was declared effective on November 14, 2023 by the U.S. Securities and Exchange Commission (the "SEC"). The offering is being made only by means of a preliminary prospectus supplement and the accompanying prospectus. A preliminary prospectus supplement and the accompany prospectus relating to the offering will be filed with the SEC and will be available on the SEC’s website at www.sec.gov. Copies of the preliminary prospectus supplement and the accompany prospectus relating to the offering, when available, may be obtained from the offices of TD Securities (USA) LLC, 1 Vanderbilt Avenue, New York, New York 10017, by email at [email protected] or by telephone at (855) 495-9846; Cantor Fitzgerald & Co., 110 East 59th Street, 6th Floor, New York, New York 10022, Attention: Capital Markets, or by email at [email protected]; or LifeSci Capital LLC, 1700 Broadway, 40th Floor, New York, New York 10019, or by email at [email protected].

Before investing in the offering, interested parties should read the preliminary prospectus supplement and related prospectus for this offering, the documents incorporated by reference therein and the other documents Protara has filed with the Securities and Exchange Commission. The final terms of the offering will be disclosed in a final prospectus supplement to be filed with the Securities and Exchange Commission.

This press release shall not constitute an offer to sell or a solicitation of an offer to buy any of these securities, nor shall there be any sale of these securities in any state or jurisdiction in which such an offer, solicitation or sale would be unlawful prior to registration or qualification under the applicable securities laws of such state or jurisdiction.

On December 9, 2024 Mendus AB ("Mendus" publ; IMMU.ST), a biopharmaceutical company focused on immunotherapies addressing tumor recurrence, reported that it has presented positive survival data from the ongoing ADVANCE II Phase 2 trial at the ASH (Free ASH Whitepaper) 2024 conference (Press release, mendus, DEC 9, 2024, View Source [SID1234648904]). The data showed that the majority of AML patients treated with vididencel remain alive and disease-free in long-term follow-up, with a median follow-up of 41.8 months.

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AML is an aggressive blood-borne tumor which requires immediate chemotherapy to reduce the level of malignant blasts in bone marrow and blood. After chemotherapy, the risk of disease relapse due to residual cancer cells is high and the only potentially curative approach in AML is a hematopoietic stem cell transplant (HSCT, or "bone marrow transplant"). Mendus’ lead product vididencel is designed to stimulate active immunity against residual cancer cells. Active immunity, built up by the patient’s immune system, is the only long-lasting form of immunity. Mendus is developing vididencel as a maintenance therapy in AML, in order to improve disease-free and overall survival in patients who are in first complete remission following first-line chemotherapy.

"We are encouraged by the updated survival data presented at ASH (Free ASH Whitepaper) confirming that the majority of patients treated with vididencel as part of the ADVANCE II trial are alive today at a median follow-up of 41.8 months, with all patients having passed 3-year follow-up and two patients already 5-year follow-up." said Erik Manting, CEO of Mendus. "These data mark a significant milestone for Mendus, and support our accelerated preparations for a registration trial, bringing vidicencel to the final development stage before it can broadly reach patients in need. In parallel, we will look for opportunities to initiate additional trials, such as the ongoing AMLM22-CADENCE trial evaluating vididencel with oral azacitidine, in collaboration with the Australasian Leukaemia and Lymphoma Group. The preclinical data presented at ASH (Free ASH Whitepaper) further support the broader exploration of vididencel as a maintenance therapy in AML and potentially other blood-borne tumors, such as CML."

ADVANCE II data presented at ASH (Free ASH Whitepaper)
The ADVANCE II Phase 2 trial is an international multi-center Phase 2 trial evaluating vididencel as maintenance treatment for AML patients in first complete remission (CR1) following chemotherapy. Patients participating in the trial were ineligible for HSCT and had measurable residual disease (MRD), which is associated with increased relapse rates. The ADVANCE II trial has completed the active study phase of 70-week follow-up from the start of vididencel treatment and patients are now in long-term follow up.

The updated ADVANCE II data presented at ASH (Free ASH Whitepaper) show that 13 out of 20 patients treated with vididencel were alive and 11 patients were still in CR1 as of the November 4, 2024 cut-off-date, with a median follow-up of 41.8 months. Median relapse-free (RFS) and overall survival (OS) was not reached, as the majority of patients remained alive and disease-free. All patients had passed 3-year follow-up and 2 patients completed 5-year follow-up. The 1-year survival stood at 88%, 3-year survival at 71% and the estimated 5-year survival was 58%.

The only drug approved for post-chemo AML maintenance therapy is oral azacitidine, which in MRD-positive patients led to a median RFS of 7.1 months and a median OS of 14.6 months in the registration trial1. The estimated 3-year OS for the whole treated patient population which included MRD-positive and -negative patients was 37.4% and 5-year OS was 26.5%2.

(1Roboz et al. (2022) Blood; 139(4):2145, 2Wei et al., (2023) Am J Hematol 98: E84)

Immunomonitoring data from the ADVANCE II trial presented at ASH (Free ASH Whitepaper) demonstrated that patients with multiple T cell responses following vididencel treatment (sustained vaccine-induced responses, or sVIR) had a significantly better OS than patients without a sVIR (p=0.036) and a higher number of MRD responses, with 6 our of 9 patients showing MRD clearance or > 10-fold reduction in MRD level. There were also clear differences between patient groups at baseline. Particularly patients with high levels of B cells and low levels of inhibitory T cells showed significantly improved OS (p=0.0109) and the majority of these patients (6 out of 8) demonstrated sVIR following vididencel treatment. The data confirm that vididencel stimulates a broad, active immune response against residual disease, which is associated with improved clinical outcome.

"The data presented at ASH (Free ASH Whitepaper) confirm that vididencel acts as an active immunotherapy against residual cancer cells and has the potential to deliver durable clinical responses in AML. Combined with a strong safety profile, we believe this makes vididencel one of the most promising maintenance treatments currently in development in AML." said Jeroen Rovers, CMO of Mendus. "Based on the positive ADVANCE II data, we are executing on a clinical trial strategy aimed at market registration of vididencel in AML, while exploring opportunities to broaden the addressable patient population."

Other abstracts presented at ASH (Free ASH Whitepaper)
In addition to the ADVANCE II Phase 2 trial data in the post-chemotherapy maintenance setting, Mendus presented two abstracts based on preclinical data exploring the use of vididencel in additional patient populations. AML patients ineligible for high-intensity chemotherapy can be treated today with a combination of azacitidine (AZA) and venetoclax (VEN). In vitro data demonstrated that AZA and VEN do not interfere with vididencel’s mode of action and that VEN stimulates the processing of vididencel by antigen-presenting cells. In vivo data confirmed that vididencel and AZA+VEN act synergistically in a humanized mouse model for AML, supporting the clinical exploration of vididencel in AML patients treated with AZA+VEN. The second preclinical abstract addressed the potential use of vididencel in chronic myeloid leukemia (CML). Data showed that vididencel can stimulate cellular immunity against a CML cell line and investigated the combination potential of vididencel with different tyrosine kinase inhibitor drugs currently used for the treatment of CML. The possibility to improve immunity against residual cancer cells with vididencel addresses the need to improve treatment-free remission rates, allowing CML patients to control their disease without the need for life-long medication.
All data presented at ASH (Free ASH Whitepaper) are available on the Mendus corporate website via View Source